The present invention relates to methods for forming, particularly for shaping and/or depositing, cell material having multiple biological cells, particularly methods for setting or changing a surface topography of a cell material and methods for geometrical structuring of cell material, such as methods for tissue engineering. The present invention also relates to manipulation tools for performing these methods, particularly substrates for cell material, such as cell cultures or tissue, and shaping tools, using which the geometrical shape and/or dimensions of the cell material are changeable. The present invention also relates to novel applications of the cited methods and manipulation tools.
In medicine, biotechnology, and biochemistry, essential objects exist in the examination or manipulation of biological cells, particularly in connection with medicinal cell therapy and tissue engineering, in that cell formations or cell groups are provided having a predefined geometrical arrangement of the individual cells. For example, the shape of a cell material which is implanted into an organism is to be tailored as well as possible to the geometrical conditions at the implantation location. Adapting the shape of the implant material by suitable mechanical trimming (cutting) from a cell culture is known from practice. However, this is disadvantageous since damage to the cells or the cell material may have undesired effects during the tissue regeneration after the implantation. In numerous experiments known from practice, the desired regeneration or new growth of a cell or tissue type did not occur, but rather, for example, an induction of tumors. It is assumed that induction of tumors as uncontrolled cell reproduction of cells, is encouraged by physical, chemical, or mechanical external influences at the implant location. These influences may not be implemented reproducibly or at least detected using the current technologies.
A further example of the shaping of cell material is the examination of active ingredients (testing of pharmacological active ingredients) on tissue models. Preferably, spheroids are used as tissue models, which may be produced as spherical formations through layered growth of cell material on an inner core made of cells. A disadvantage of conventional tissue models is their restricted size. For example, until now only spheroids up to a diameter of approximately 150 μm have been able to be used. At larger diameters, problems arise in the nutrient supply of the inner cells. The vitality of the inner cells is restricted and dying of the cells from the inside to the outside may occur.
A further object in tissue engineering which has not been achieved up to this point is the production of structured composite material from cell materials of different types of cells or from biological cells and synthetic materials. A disadvantage is that up to now composite formations have been associated with mechanical injuries of cells or cell material.
The objects cited in cell therapy and the results in tissue engineering, which have been partially unsatisfactory up to this point, currently represent the most important restrictions and delays of a broad application of these methods in biotechnology and medicine.
The object of the present invention is to provide improved methods for forming cell material having a predefined geometrical arrangement of the individual cells, using which the disadvantages of conventional methods are overcome and which are particularly capable of shaping and/or generating cell material without injuring individual cells. It is also the object of the present invention to provide improved manipulation tools for performing methods of this type, using which the disadvantages of conventional cell or tissue technologies are overcome. It is a further object of the present invention to specify novel applications of the shaping, cultivation, or generation of cell material.
These objects are achieved by methods and manipulation tools having the features of the present invention.